Visuo-frontal interactions during social learning in freely moving macaques.

Social interactions represent a ubiquitous aspect of our everyday life that we acquire by interpreting and responding to visual cues from conspecifics1. However, despite the general acceptance of this view, how visual information is used to guide the decision to cooperate is unknown. Here, we wirelessly recorded the spiking activity of populations of neurons in the visual and prefrontal cortex in conjunction with wireless recordings of oculomotor events while freely moving macaques engaged in social cooperation. As animals learned to cooperate, visual and executive areas refined the representation of social variables, such as the conspecific or reward, by distributing socially relevant information among neurons in each area. Decoding population activity showed that viewing social cues influences the decision to cooperate. Learning social events increased coordinated spiking between visual and prefrontal cortical neurons, which was associated with improved accuracy of neural populations to encode social cues and the decision to cooperate. These results indicate that the visual-frontal cortical network prioritizes relevant sensory information to facilitate learning social interactions while freely moving macaques interact in a naturalistic environment.

Computational modeling and minimization of unintended neuronal excitation in a LIFU stimulation.

The neuromodulation effect of low-intensity focused ultrasound (LIFU) is highly target-specific. Unintended off-target neuronal excitation can be elicited when the beam focusing accuracy and resolution are limited, whereas the resulted side effect has not been evaluated quantitatively. There is also a lack of methods addressing the minimization of such side effects. Therefore, this work introduces a computational model of unintended neuronal excitation during LIFU neuromodulation, which evaluates the off-target activation area (OTAA) by integrating an ultrasound field model with the neuronal spiking model. In addition, a phased array beam focusing scheme called constrained optimal resolution beamforming (CORB) is proposed to minimize the off-target neuronal excitation area while ensuring effective stimulation in the target brain region. A lower bound of the OTAA is analytically approximated in a simplified homogeneous medium, which could guide the selection of transducer parameters such as aperture size and operating frequency. Simulations in a human head model using three transducer setups show that CORB markedly reduces the OTAA compared with two benchmark beam focusing methods. The high neuromodulation resolution demonstrates the capability of LIFU to effectively limit the side effects during neuromodulation, allowing future clinical applications such as treatment of neuropsychiatric disorders.

Sub-scalp electroencephalography: A next-generation technique to study human neurophysiology.

Sub-scalp electroencephalography (ssEEG) is emerging as a promising technology in ultra-long-term electroencephalography (EEG) recordings. Given the diversity of devices available in this nascent field, uncertainty persists about its utility in epilepsy evaluation. This review critically dissects the many proposed utilities of ssEEG devices including (1) seizure quantification, (2) seizure characterization, (3) seizure lateralization, (4) seizure localization, (5) seizure alarms, (6) seizure forecasting, (7) biomarker discovery, (8) sleep medicine, and (9) responsive stimulation. The different ssEEG devices in development have individual design philosophies with unique strengths and limitations. There are devices offering primarily unilateral recordings (24/7 EEGTM SubQ, NeuroviewTM, Soenia® UltimateEEG™), bilateral recordings (Minder™, Epios™), and even those with responsive stimulation capability (EASEE®). We synthesize the current knowledge of these ssEEG systems. We review the (1) ssEEG devices, (2) use case scenarios, (3) challenges and (4) suggest a roadmap for ideal ssEEG designs.

RT-RCG: Neural Network and Accelerator Search Towards Effective and Real-time ECG Reconstruction from Intracardiac Electrograms.

There exists a gap in terms of the signals provided by pacemakers (i.e., intracardiac electrogram (EGM)) and the signals doctors use (i.e., 12-lead electrocardiogram (ECG)) to diagnose abnormal rhythms. Therefore, the former, even if remotely transmitted, are not sufficient for doctors to provide a precise diagnosis, let alone make a timely intervention. To close this gap and make a heuristic step towards real-time critical intervention in instant response to irregular and infrequent ventricular rhythms, we propose a new framework dubbed RT-RCG to automatically search for (1) efficient Deep Neural Network (DNN) structures and then (2) corresponding accelerators, to enable Real-Time and high-quality Reconstruction of ECG signals from EGM signals. Specifically, RT-RCG proposes a new DNN search space tailored for ECG reconstruction from EGM signals, and incorporates a differentiable acceleration search (DAS) engine to efficiently navigate over the large and discrete accelerator design space to generate optimized accelerators. Extensive experiments and ablation studies under various settings consistently validate the effectiveness of our RT-RCG. To the best of our knowledge, RT-RCG is the first to leverage neural architecture search (NAS) to simultaneously tackle both reconstruction efficacy and efficiency.

EMvelop stimulation: minimally invasive deep brain stimulation using temporally interfering electromagnetic waves.

Objective.Recently, the temporal interference stimulation (TIS) technique for focal noninvasive deep brain stimulation (DBS) was reported. However, subsequent computational modeling studies on the human brain have shown that while TIS achieves higher focality of electric fields than state-of-the-art methods, further work is needed to improve the stimulation strength. Here, we investigate the idea of EMvelop stimulation, a minimally invasive DBS setup using temporally interfering gigahertz (GHz) electromagnetic (EM) waves. At GHz frequencies, we can create antenna arrays at the scale of a few centimeters or less that can be endocranially implanted to enable longitudinal stimulation and circumvent signal attenuation due to the scalp and skull. Furthermore, owing to the small wavelength of GHz EM waves, we can optimize both amplitudes and phases of the EM waves to achieve high intensity and focal stimulation at targeted regions within the safety limit for exposure to EM waves.Approach.We develop a simulation framework investigating the propagation of GHz EM waves generated by line current antenna elements and the corresponding heat generated in the brain tissue. We propose two optimization flows to identify antenna current amplitudes and phases for either maximal intensity or maximal focality transmission of the interfering electric fields with EM waves safety constraint.Main results.A representative result of our study is that with two endocranially implanted arrays of size4.2 cm×4.7 cmeach, we can achieve an intensity of 12 V m-1with a focality of3.6 cmat a target deep in the brain tissue.Significance.In this proof-of-principle study, we show that the idea of EMvelop stimulation merits further investigation as it can be a minimally invasive way of stimulating deep brain targets and offers benefits not shared by prior methodologies of electrical or magnetic stimulation.

Epileptic electroencephalography classification using Embedded Dynamic Mode Decomposition.

OBJECTIVE: Seizure prediction devices for drug-resistant epileptic patients could lead to improved quality of life and new treatment options, but current approaches to classification of electroencephalography (EEG) segments for early identification of the pre-seizure state typically require many features and complex classifiers. We therefore propose a novel spatio-temporal EEG feature set that significantly aids in separation and easy classification of the interictal and preictal states. APPROACH: We derive key spectral features from the Embedded Dynamic Mode Decomposition (EmDMD) of the brain state system. This method linearizes the complex spatio-temporal dynamics of the system, describing the dynamics in terms of a spectral basis of modes and eigenvalues. The relative subband spectral power and mean phase locking values of these modes prove to be good indicators of the preictal state that precedes seizure onset. MAIN RESULTS: We analyze the linear separability and classification of preictal and interictal states based on our proposed features using seizure data extracted from the CHB-MIT scalp EEG and Kaggle American Epilepsy Society Seizure Prediction Challenge intracranial EEG databases. With a light-weight support vector machine or random forest classifier trained on these features, we classify the preictal state with a sensitivity of up to 92% and specificity of up to 89%. SIGNIFICANCE: The EmDMD-derived features separate the preictal and interictal states, improving classification accuracy and motivating further work to incorporate them into seizure prediction algorithms.

Manifold Approximating Graph Interpolation of Cardiac Local Activation Time.

OBJECTIVE: Local activation time (LAT) mapping of cardiac chambers is vital for targeted treatment of cardiac arrhythmias in catheter ablation procedures. Current methods require too many LAT observations for an accurate interpolation of the necessarily sparse LAT signal extracted from intracardiac electrograms (EGMs). Additionally, conventional performance metrics for LAT interpolation algorithms do not accurately measure the quality of interpolated maps. We propose, first, a novel method for spatial interpolation of the LAT signal which requires relatively few observations; second, a realistic sub-sampling protocol for LAT interpolation testing; and third, a new color-based metric for evaluation of interpolation quality that quantifies perceived differences in LAT maps. METHODS: We utilize a graph signal processing framework to reformulate the irregular spatial interpolation problem into a semi-supervised learning problem on the manifold with a closed-form solution. The metric proposed uses a color difference equation and color theory to quantify visual differences in generated LAT maps. RESULTS: We evaluate our approach on a dataset consisting of seven LAT maps from four patients obtained by the CARTO electroanatomic mapping system during premature ventricular complex (PVC) ablation procedures. Random sub-sampling and re-interpolation of the LAT observations show excellent accuracy for relatively few observations, achieving on average 6% lower error than state-of-the-art techniques for only 100 observations. CONCLUSION: Our study suggests that graph signal processing methods can improve LAT mapping for cardiac ablation procedures. SIGNIFICANCE: The proposed method can reduce patient time in surgery by decreasing the number of LAT observations needed for an accurate LAT map.

Artificial Intelligence and Machine Learning in Cardiac Electrophysiology.

Cardiac electrophysiology requires the processing of several patient-specific data points in real time to provide an accurate diagnosis and determine an optimal therapy. Expanding beyond the traditional tools that have been used to extract information from patient-specific data, machine learning offers a new set of advanced tools capable of revealing previously unknown data patterns and features. This new tool set can substantially improve the speed and level of confidence with which electrophysiologists can determine patient-specific diagnoses and therapies. The ability to process substantial amounts of data in real time also paves the way to novel techniques for data collection and visualization. Extended realities such as virtual and augmented reality can now enable the real-time visualization of 3-dimensional images in space. This enables improved preprocedural planning and intraprocedural interventions. Machine learning supplemented with novel visualization technologies could substantially improve patient care and outcomes by helping physicians to make more informed patient-specific decisions. This article presents current applications of machine learning and their use in cardiac electrophysiology.

Epileptic seizure prediction using spectral width of the covariance matrix.

Objective.Epilepsy is a common neurological disorder in which patients suffer from sudden and unpredictable seizures. Seizures are caused by excessive and abnormal neuronal activity. Different methods have been employed to investigate electroencephalogram (EEG) data in patients with epilepsy. This paper introduces a simple yet accurate array-based method to study and predict seizures.Approach.We use the CHB-MIT dataset (all 24 cases), which includes scalp EEG recordings. The proposed method is based on the random matrix theory. After applying wavelet decomposition to denoise the data, we analyze the spatial coherence of the epileptic recordings by looking at the width of the covariance matrix eigenvalue distribution at different time and frequency bins.Main results.We train patient-specific support vector machine classifiers to distinguish between interictal and preictal data with high performance and a false prediction rate as low as 0.09 h-1. The proposed technique achieves an average accuracy, specificity, sensitivity, and area under the curve of 99.05%, 93.56%, 99.09%, and 0.99, respectively.Significance.Our proposed method outperforms state-of-the-art works in terms of sensitivity while maintaining a low false prediction rate. Also, in contrast to neural networks, which may achieve high performance, this work provides high sensitivity without compromising interpretability.

A novel convolutional neural network for reconstructing surface electrocardiograms from intracardiac electrograms and vice versa.

We propose a novel convolutional neural network framework for mapping a multivariate input to a multivariate output. In particular, we implement our algorithm within the scope of 12-lead surface electrocardiogram (ECG) reconstruction from intracardiac electrograms (EGM) and vice versa. The goal of performing this task is to allow for improved point-of-care monitoring of patients with an implanted device to treat cardiac pathologies. We will achieve this goal with 12-lead ECG reconstruction and by providing a new diagnostic tool for classifying five different ECG types. The algorithm is evaluated on a dataset retroactively collected from 14 patients. Correlation coefficients calculated between the reconstructed and the actual ECG show that the proposed convolutional neural network model represents an efficient, accurate, and superior way to synthesize a 12-lead ECG when compared to previous methods. We can also achieve the same reconstruction accuracy with only one EGM lead as input. We also tested the model in a non-patient specific way and saw a reasonable correlation coefficient. The model was also executed in the reverse direction to produce EGM signals from a 12-lead ECG and found that the correlation was comparable to the forward direction. Lastly, we analyzed the features learned in the model and determined that the model learns an overcomplete basis of our 12-lead ECG space. We then use this basis of features to create a new diagnostic tool for classifying different ECG arrhythmia's on the MIT-BIH arrhythmia database with an average accuracy of 0.98.

Review of wearable technologies and machine learning methodologies for systematic detection of mild traumatic brain injuries.

Mild traumatic brain injuries (mTBIs) are the most common type of brain injury. Timely diagnosis of mTBI is crucial in making 'go/no-go' decision in order to prevent repeated injury, avoid strenuous activities which may prolong recovery, and assure capabilities of high-level performance of the subject. If undiagnosed, mTBI may lead to various short- and long-term abnormalities, which include, but are not limited to impaired cognitive function, fatigue, depression, irritability, and headaches. Existing screening and diagnostic tools to detect acute andearly-stagemTBIs have insufficient sensitivity and specificity. This results in uncertainty in clinical decision-making regarding diagnosis and returning to activity or requiring further medical treatment. Therefore, it is important to identify relevant physiological biomarkers that can be integrated into a mutually complementary set and provide a combination of data modalities for improved on-site diagnostic sensitivity of mTBI. In recent years, the processing power, signal fidelity, and the number of recording channels and modalities of wearable healthcare devices have improved tremendously and generated an enormous amount of data. During the same period, there have been incredible advances in machine learning tools and data processing methodologies. These achievements are enabling clinicians and engineers to develop and implement multiparametric high-precision diagnostic tools for mTBI. In this review, we first assess clinical challenges in the diagnosis of acute mTBI, and then consider recording modalities and hardware implementation of various sensing technologies used to assess physiological biomarkers that may be related to mTBI. Finally, we discuss the state of the art in machine learning-based detection of mTBI and consider how a more diverse list of quantitative physiological biomarker features may improve current data-driven approaches in providing mTBI patients timely diagnosis and treatment.

Inferring functional connectivity through graphical directed information.

Objective. Accurate inference of functional connectivity is critical for understanding brain function. Previous methods have limited ability distinguishing between direct and indirect connections because of inadequate scaling with dimensionality. This poor scaling performance reduces the number of nodes that can be included in conditioning. Our goal was to provide a technique that scales better and thereby enables minimization of indirect connections.Approach. Our major contribution is a powerful model-free framework, graphical directed information (GDI), that enables pairwise directed functional connections to be conditioned on the activity of substantially more nodes in a network, producing a more accurate graph of functional connectivity that reduces indirect connections. The key technology enabling this advancement is a recent advance in the estimation of mutual information (MI), which relies on multilayer perceptrons and exploiting an alternative representation of the Kullback-Leibler divergence definition of MI. Our second major contribution is the application of this technique to both discretely valued and continuously valued time series.Main results. GDI correctly inferred the circuitry of arbitrary Gaussian, nonlinear, and conductance-based networks. Furthermore, GDI inferred many of the connections of a model of a central pattern generator circuit inAplysia, while also reducing many indirect connections.Significance. GDI is a general and model-free technique that can be used on a variety of scales and data types to provide accurate direct connectivity graphs and addresses the critical issue of indirect connections in neural data analysis.

Addressing indirect frequency coupling via partial generalized coherence.

Distinguishing between direct and indirect frequency coupling is an important aspect of functional connectivity analyses because this distinction can determine if two brain regions are directly connected. Although partial coherence quantifies partial frequency coupling in the linear Gaussian case, we introduce a general framework that can address even the nonlinear and non-Gaussian case. Our technique, partial generalized coherence (PGC), expands prior work by allowing pairwise frequency coupling analyses to be conditioned on other processes, enabling model-free partial frequency coupling results. By taking advantage of recent advances in conditional mutual information estimation, we are able to implement our technique in a way that scales well with dimensionality, making it possible to condition on many processes and produce a partial frequency coupling graph. We analyzed both linear Gaussian and nonlinear simulated networks. We then performed PGC analysis of calcium recordings from mouse olfactory bulb glomeruli under anesthesia and quantified the dominant influence of breathing-related activity on the pairwise relationships between glomeruli for breathing-related frequencies. Overall, we introduce a technique capable of eliminating indirect frequency coupling in a model-free way, empowering future research to correct for potentially misleading frequency interactions in functional connectivity analyses.

NetDI: Methodology Elucidating the Role of Power and Dynamical Brain Network Features That Underpin Word Production.

Canonical language models describe eloquent function as the product of a series of cognitive processes, typically characterized by the independent activation profiles of focal brain regions. In contrast, more recent work has suggested that the interactions between these regions, the cortical networks of language, are critical for understanding speech production. We investigated the cortical basis of picture naming (PN) with human intracranial electrocorticography (ECoG) recordings and direct cortical stimulation (DCS), adjudicating between two competing hypotheses: are task-specific cognitive functions discretely computed within well-localized brain regions or rather by distributed networks? The time resolution of ECoG allows direct comparison of intraregional activation measures [high gamma (h γ ) power] with graph theoretic measures of interregional dynamics. We developed an analysis framework, network dynamics using directed information (NetDI), using information and graph theoretic tools to reveal spatiotemporal dynamics at multiple scales: coarse, intermediate, and fine. Our analysis found novel relationships between the power profiles and network measures during the task. Furthermore, validation using DCS indicates that such network parameters combined with hγ power are more predictive than hγ power alone, for identifying critical language regions in the brain. NetDI reveals a high-dimensional space of network dynamics supporting cortical language function, and to account for disruptions to language function observed after neurosurgical resection, traumatic injury, and degenerative disease.

Precise measurement of correlations between frequency coupling and visual task performance.

Functional connectivity analyses focused on frequency-domain relationships, i.e. frequency coupling, powerfully reveal neurophysiology. Coherence is commonly used but neural activity does not follow its Gaussian assumption. The recently introduced mutual information in frequency (MIF) technique makes no model assumptions and measures non-Gaussian and nonlinear relationships. We develop a powerful MIF estimator optimized for correlating frequency coupling with task performance and other relevant task phenomena. In light of variance reduction afforded by multitaper spectral estimation, which is critical to precisely measuring such correlations, we propose a multitaper approach for MIF and compare its performance with coherence in simulations. Additionally, multitaper MIF and coherence are computed between macaque visual cortical recordings and their correlation with task performance is analyzed. Our multitaper MIF estimator produces low variance and performs better than all other estimators in simulated correlation analyses. Simulations further suggest that multitaper MIF captures more information than coherence. For the macaque data set, coherence and our new MIF estimator largely agree. Overall, we provide a new way to precisely estimate frequency coupling that sheds light on task performance and helps neuroscientists accurately capture correlations between coupling and task phenomena in general. Additionally, we make an MIF toolbox available for the first time.

Recent Advances in Electrical Neural Interface Engineering: Minimal Invasiveness, Longevity, and Scalability.

Electrical neural interfaces serve as direct communication pathways that connect the nervous system with the external world. Technological advances in this domain are providing increasingly more powerful tools to study, restore, and augment neural functions. Yet, the complexities of the nervous system give rise to substantial challenges in the design, fabrication, and system-level integration of these functional devices. In this review, we present snapshots of the latest progresses in electrical neural interfaces, with an emphasis on advances that expand the spatiotemporal resolution and extent of mapping and manipulating brain circuits. We include discussions of large-scale, long-lasting neural recording; wireless, miniaturized implants; signal transmission, amplification, and processing; as well as the integration of interfaces with optical modalities. We outline the background and rationale of these developments and share insights into the future directions and new opportunities they enable.

Estimating the Memory Order of Electrocorticography Recordings.

OBJECTIVE: This paper presents a data-driven method for estimating the memory order (the average length of the statistical dependence of a given sample on previous samples) of a recorded electrocorticography (ECoG) sequence. METHODS: The proposed inference method is based on the relationship between the loss in predicting the next sample in a time-series and the dependence of this sample on the previous samples. Specifically, the memory order is estimated to be the number of past samples that minimize the least squares error (LSE) in predicting the next sample. To deal with the lack of an analytical model for ECoG recordings, the proposed method combines a collection of different predictors, thereby achieving LSE at least as low as the LSE achieved by each of the different predictors. RESULTS: ECoG recordings from six patients with epilepsy were analyzed, and the empirical cumulative density functions (ECDFs) of the memory orders estimated from these recordings were generated, for rest as well as pre-ictal time intervals. For pre-ictal time intervals, the electrodes corresponding to the seizure-onset-zone were separately analyzed. The estimated ECDFs were different between patients and between different types of blocks. For all the analyzed patients, the estimated memory orders were on the order of tens of milliseconds (up to 100 ms). SIGNIFICANCE: The proposed method facilitates the estimation of the causal associations between ECoG recordings, as these associations strongly depend on the recordings' memory. An improved estimation of causal associations can improve the performance of algorithms that use ECoG recordings to localize the epileptogenic zone. Such algorithms can aid doctors in their pre-surgical planning for the surgery of patients with epilepsy.

The interictal mesial temporal lobe epilepsy network.

OBJECTIVE: Identification of patient-specific epileptogenic networks is critical to designing successful treatment strategies. Multiple noninvasive methods have been used to characterize epileptogenic networks. However, these methods lack the spatiotemporal resolution to allow precise localization of epileptiform activity. We used intracranial recordings, at much higher spatiotemporal resolution, across a cohort of patients with mesial temporal lobe epilepsy (MTLE) to delineate features common to their epileptogenic networks. We used interictal rather than seizure data because interictal spikes occur more frequently, providing us greater power for analyzing variances in the network. METHODS: Intracranial recordings from 10 medically refractory MTLE patients were analyzed. In each patient, hour-long recordings were selected for having frequent interictal discharges and no ictal events. For all possible pairs of electrodes, conditional probability of the occurrence of interictal spikes within a 150-millisecond bin was computed. These probabilities were used to construct a weighted graph between all electrodes, and the node degree was estimated. To assess the relationship of the highly connected regions in this network to the clinically identified seizure network, logistic regression was used to model the regions that were surgically resected using weighted node degree and number of spikes in each channel as factors. Lastly, the conditional spike probability was normalized and averaged across patients to visualize the MTLE network at group level. RESULTS: We generated the first graph of connectivity across a cohort of MTLE patients using interictal activity. The most consistent connections were hippocampus to amygdala, anterior fusiform cortex to hippocampus, and parahippocampal gyrus projections to amygdala. Additionally, the weighted node degree and number of spikes modeled the brain regions identified as seizure networks by clinicians. SIGNIFICANCE: Apart from identifying interictal measures that can model patient-specific epileptogenic networks, we also produce a group map of network connectivity from a cohort of MTLE patients.

Inferring neuronal network functional connectivity with directed information.

A major challenge in neuroscience is to develop effective tools that infer the circuit connectivity from large-scale recordings of neuronal activity patterns. In this study, context tree maximizing (CTM) was used to estimate directed information (DI), which measures causal influences among neural spike trains in order to infer putative synaptic connections. In contrast to existing methods, the method presented here is data driven and can readily identify both linear and nonlinear relations between neurons. This CTM-DI method reliably identified circuit structures underlying simulations of realistic conductance-based networks. It also inferred circuit properties from voltage-sensitive dye recordings of the buccal ganglion of Aplysia. This method can be applied to other large-scale recordings as well. It offers a systematic tool to map network connectivity and to track changes in network structure such as synaptic strengths as well as the degrees of connectivity of individual neurons, which in turn could provide insights into how modifications produced by learning are distributed in a neural network.NEW & NOTEWORTHY This study brings together the techniques of voltage-sensitive dye recording and information theory to infer the functional connectome of the feeding central pattern generating network of Aplysia. In contrast to current statistical approaches, the inference method developed in this study is data driven and validated by conductance-based model circuits, can distinguish excitatory and inhibitory connections, is robust against synaptic plasticity, and is capable of detecting network structures that mediate motor patterns.